Study of association of serum bicarbonate levels with mortality in chronic kidney disease

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1 International Journal of Research in Medical Sciences Kumar S et al. Int J Res Med Sci Nov;4(11): pissn eissn Original Research Article DOI: Study of association of serum bicarbonate levels with mortality in chronic kidney disease Kumar S. 1 *, Nikethan D. 2 1 Associate Professor, Department of General Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India 2 Department of General Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India Received: 26 August 2016 Revised: 30 August 2016 Accepted: 27 September 2016 *Correspondence: Dr. Kumar S., kumarsrinivasan67@gmail.com Copyright: the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background: Chronic kidney disease has been recognized as a major global public health problem. The approximate prevalence of CKD in India is 800 per million population. Metabolic acidosis is a feature of CKD due to the reduced capacity of the kidney to synthesise ammonia and excrete hydrogen ions. This may be corrected by oral bicarbonate supplementation or by increasing the bicarbonate concentration in the dialysate fluid during dialysis. Studies have shown that low serum bicarbonate is associated with progression of kidney disease and increased mortality. Due to the limited availability of studies done in Indian population this study was undertaken to assess the serum bicarbonate levels in different stages of CKD and its effect. Methods: Prospective data of 100 patients with various stages of chronic kidney disease admitted and treated in vims hospital in department of medicine and nephrology between January 2014 to June 2015 were studied. Results: out of 100 cases 71 were male and 29 were female. Highest numbers of cases were found in the age group of 51 to 60 years followed by 41 to 50yrs. Most common cause of chronic kidney disease in our study group were diabetes, hypertension, nephrotic syndrome PCKD. Most patients were in stage 4 followed by stage 2, and Many patients had low serum bicarbonate level and only 07 patients had high serum bicarbonate level who were in stage 3 and stage 4. Of the 21 mortality 14 patients had low serum bicarbonate level (10-14 meq/l) and 07 patients had high serum bicarbonate level (mean value 25 meq/l). More death were noticed in the stage 5 followed stage 4 and stage 3 in 6th decade. Out of 100 cases, 68 cases were on dialysis and 32 cases were not on dialysis. Hence present study determines the association of serum bicarbonate levels as a risk factor for mortality in chronic kidney disease. Conclusions: low serum bicarbonate levels are associated with high mortality in chronic kidney disease. Hence it is essential to optimise serum bicarbonates with oral supplementation. Keywords: Chronic kidney disease, Metabolic acidosis, Serum bicarbonates INTRODUCTION Chronic kidney disease has been recognized as a major global public health problem. The approximate prevalence of CKD in India is 800 per million population. 1 Prevalence of CKD patients will continue to rise, reflecting the growing elderly population and increasing number of patients with diabetes and hypertension. 1,2 Metabolic acidosis is a feature of CKD due to the reduced capacity of the kidney to synthesize ammonia and excrete hydrogen ions. This may be corrected by oral bicarbonate supplementation or by increasing the bicarbonate concentration in the dialysate fluid during dialysis. 3 Normally an approximate of 15,000 International Journal of Research in Medical Sciences November 2016 Vol 4 Issue 11 Page 4852

2 mmol of carbon dioxide and 50 to 100 mleq of nonvolatile acid is produced each day. Acid-base balance is maintained by elimination of carbon dioxide by the lungs and excretion of nonvolatile acid by the kidneys which affects the plasma bicarbonate concentration. 4 The hydrogen ion concentration of the blood is determined by the ratio of the pco 2 and plasma bicarbonate concentration. Metabolic acidosis can be due to one or more of the following pathophysiologic processes such as increased production of nonvolatile acids, increased loss of bicarbonate and decreased renal excretion of acid. 5 In chronic kidney disease metabolic acidosis occurs due to an impairment of ammonium excretion as a result of decreased functioning nephrons where the total ammonium excretion begins to fall when the glomerular filtration rate (GFR) is below 40 to 50 ml/min. The retained acid is buffered by bicarbonate in the extracellular fluid, by tissue buffers, and by bone. Usually the anion gap remains normal until late stages of CKD when it begins to widen due to the retention of anions such as phosphate, sulfate, urate, and hippurate. Renal replacement therapy improves metabolic acidosis due to the additional base load delivered in the dialysate. 6,7 Studies have shown that low serum bicarbonate is associated with progression of kidney disease and increased mortality. 8 Due to the limited availability of studies done in Indian population this study was undertaken to assess the serum bicarbonate levels in different stages of CKD and its effect. METHODS Prospective data of 100 patients with various stages of chronic kidney disease admitted and treated in VIMS&RC hospital in department of Medicine and Nephrology between January 2014 to June 2015 were studied as per proforma and after obtaining their consent. The institutional ethics committee approved the study. Objective Patients were observed for levels of serum bicarbonate at various stages of CKD and their association with mortality during the hospital stay. Inclusion criteria All CKD patients aged > eighteen years stage-2-4 with or without dialysis. Exclusion criteria Patients> eighteen, pregnant patients, patients with renal transplant, chronic heart disease and cancer were excluded from our study. Statistical analysis was done using SPSS 11. RESULTS Out of 100 cases 71 were male and 29 were female. Highest numbers of cases were found in the age group of 51 to 60 years, followed by 41 to 50 years. Most common cause of chronic kidney disease in our study group were diabetes, hypertension, nephrotic syndrome, Poly Cystic Kidney Disease. Most patients were in stage 4 followed by stage 2, and Many patients had low serum bicarbonate level and only 07 patients had high serum bicarbonate level who were in stage 3 and stage 4. Of the 21 mortality, 14 (66.64%) patients had low serum bicarbonate level (10-14meq/l) and 07 (33.36%) patients had high serum bicarbonate level (mean value 25meq/l). More death were noticed in the stage 5 followed stage 4 and stage 3 in the 6 th decade. Out of 100 cases, 68 cases were on dialysis and 32 cases were not on dialysis. Hence present study determines the association of serum bicarbonate levels as a risk factor for mortality in chronic kidney disease. The following were the observation made from the study of 100 cases of CKD admitted under Nephrology and Medicine Department in Vydehi Institute of Medical Science and Research Centre, Bengaluru. Table 1: Age distribution in the study group. Age in years No of cases % Percentage % % % % % % > % Total number of cases studied is 100; Mean age =58.9 years, Age range = 20 to >80 years. Table 2: Gender distribution in the study group. Sex No of Cases Percentage Male 71 71% Female 29 29% Table 3: Gender distribution across age group. Age (years) Female Percentage Male Percentage 20 to % % 31 to % % 41 to % % 51 to % % 61 to % % 71 to % % >80 0 0% % Maximum incidence of CKD occurred in the age group of years followed by in the age group of years. International Journal of Research in Medical Sciences November 2016 Vol 4 Issue 11 Page 4853

3 Majority of cases were about 71% seen in male patients, when compared to 29% seen in female patients. The common causes in the present study were diabetes mellitus, hypertension, and nephrotic syndrome. Table 4: Causes of chronic kidney disease in the study group. Diagnosis No of cases Percentage Diabetes 76 76% Hypertension 67 67% DM+HTN 52 52% Nephrotic syndrome 08 08% Drug induced 01 01% PCKD 07 07% Table 5: Stages of CKD in the study group. Stage of CKD No of cases Percentage Stage % Stage % Stage % Stage % In our study majority of patients admitted are in stage 4 followed by stage 2. Not on Dialysis 38% In present study majority of patients admitted are with in bicarbonate range of meq/lt. Table 6: Bicarbonate level in the present study. HCO3 level in meq/l No. of cases Percentage % % % < % Table 7: Mortality in relation to age. Age intervals in years No. of death Percentage % % % % % % >80 Yrs % Maximum number of deaths occurred in 6 th decade. Table 8: Relationship between HCO 3 level and mortality. HCO 3 level Mortality Percentage 21 to % 15 to % 10 to % <10 meq/l % Maximum numbers of deaths were noticed in patients with bicarbonate range of meq/lt. Figure 1: Patients on dialysis. No. of Deaths 21% On Dialysis 62% No of Patients 100% Figure 2: Mortality. Table 9: Relationship between mortality and stages of CKD. Stages of CKD No of death Percentage Stage 2 0 0% Stage % Stage % Stage % Maximum numbers of deaths were noticed in patients with stage 5. DISCUSSION Low serum bicarbonate levels are associated with high mortality in chronic kidney disease. The optimal management of metabolic acidosis in chronic kidney disease patients including the monitoring or administration of bicarbonate has not been established yet. 1-3 However various guidelines have recommended serum bicarbonate levels to be maintained at or above twenty two mleq/ltr bicarbonate replacement therapy in International Journal of Research in Medical Sciences November 2016 Vol 4 Issue 11 Page 4854

4 chronic kidney disease is possible and easy to use making it a good option. 4,5,16 Hence it is essential to optimize serum bicarbonates with oral supplementation. 6-9 According to present study it was noted that the incidence of Chronic Kidney Disease varied from minimum age of 20 years to maximum age of 88 years (Table 1). In the present study, maximum cases were found in 6th decade followed by 5 th decade (Table 2). Seventy one were male. Patients in the age group of fifty one to sixty years and twenty nine female patients were in the age group of thirty one fifty years. Most common cause of Chronic Kidney Disease in our study includes diabetes followed by hypertension. Other causes were nephrotic syndrome and Poly Cystic Kidney Disease (Table 4). Most of the patient presented in our study group were stage 4 followed by stage 5 followed by stage 2 (Table 5). Sixty eight patients in our study underwent hemodialysis and the other thirty eight did not (Figure 7). According to our study, low serum bicarbonate levels were found in the stage 5 followed by stage 4, thirty eight patients had low serum bicarbonate (Table 6). Navaneethan et al., study stated that low serum bicarbonate level are associated with increased mortality among stage 3 patients. 6,7,9 In our study, there is increased mortality in stage 3 patients associated with low serum bicarbonate level. Same study concluded that high serum bicarbonate level are associated with increased mortality in the stage 3 and stage 4. In our study, there was increased mortality in stage 3 and stage 4 with high serum bicarbonate level (Table 8). Eliichiro Kanda et al, study stated that patient with the lowest quartile of serum bicarbonate level show a high risk of chronic kidney disease progression compared with patients with high serum bicarbonate levels In present study group, many patients were in stage 4 and stage 5 have low serum bicarbonate level. Many patients in the study group had low serum bicarbonate level and only 07 patients were having high serum bicarbonate level who were in stage 3 and stage 4. Out of 100 cases, 21 patients expired (Figure 2). In this 14 patients had low serum bicarbonate level (10-14meq/l) and 07 patients had high serum bicarbonate level(mean value 25 meq/l). More death were noticed in the stage 5 followed stage 4 and stage 3 (Table 9) More death noted on 6th decade (Figure 7). Hence present study determines the association of serum bicarbonate level with mortality in chronic kidney disease. CONCLUSION Low serum bicarbonate levels are associated with high mortality in chronic kidney disease. Bicarbonate replacement therapy in chronic kidney disease is cost effective and easy to administer. Hence it can be used as a modality to optimize serum bicarbonates with iv/oral supplementation. Funding: No funding sources Conflict of interest: None declared Ethical approval: The study was approved by the Institutional Ethics Committee REFERENCES 1. Kanda E, Ai M, Yoshida M, Kuriyama R, Shiigai T. High serum bicarbonate level within the normal range prevents the progression of CKD in elderly CKD patients. BMC Nephrology. 2013;14:4. 2. Goraya N, Simoni J, Jo CH, Wesson DE. A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate. Clin J Am Soc Nephrol. 2013;8: Yaqoob MM. Treatment of acidosis in CKD. Clin J Am Soc Nephrol. 2013;8: Saikumar JH, Kovesdy CP. Bicarbonate therapy in end-stage renal disease: current practice trends and implications. Semin Dial. 2015;28: Kovesdy CP. Metabolic acidosis and kidney disease: does bicarbonate therapy slow the progression of CKD? Nephrol Dial Transplant. 2012;27: Raphael KL, Zhang Y, Wei G. Serum bicarbonate and mortality in adults in NHANES III. 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5 16. KDIGO. Management of progression and complications of CKD. Kidney Int Suppl. 2013;3: Abramowitz MK, Melamed ML, Bauer C. Effects of oral sodium bicarbonate in patients with CKD. Clin J Am Soc Nephrol. 2013;8:714. Cite this article as: Kumar S, Nikethan D. Study of association of serum bicarbonate levels with mortality in chronic kidney disease. Int J Res Med Sci 2016;4: International Journal of Research in Medical Sciences November 2016 Vol 4 Issue 11 Page 4856